MELOE-1 is a new antigen overexpressed in melanomas and involved in adoptive T cell transfer efficiency.
A cytotoxic T lymphocyte (CTL) clone was derived from a tumor-infiltrating lymphocyte (TIL) population infused to a melanoma patient who remained relapse free for 10 yr after this adoptive transfer. This clone recognized all melanoma cell lines tested and, to a lower extent, melanocytes, in the context of human histocompatibility leukocyte antigen A2 (HLA-A2), but it did not recognize other tumor cell types. The gene coding for the antigen recognized by this clone was identified by the screening of a melanoma complementary DNA expression library. This antigen is overexpressed in melanomas, compared with other cancer cell lines and healthy tissues, and was thus called melanoma-overexpressed antigen (meloe). Remarkably, the structure of meloe was unusual, with multiple short open reading frames (ORFs). The peptide recognized by the CTL clone was encoded by one of these ORFs, called MELOE-1. Using a specific HLA-A2/peptide tetramer, we showed a correlation between the infusion of TILs containing MELOE-1-specific T cells and relapse prevention in HLA-A2 patients. Indeed, 5 out of 9 patients who did not relapse were infused with TILs that contained MELOE-1-specific T cells, whereas 0 out of the 21 patients who relapsed was infused with such TIL-containing lymphocytes. Overall, our results suggest that this new antigen is involved in immunosurveillance and, thus, represents an attractive target for immunotherapy protocols of melanoma.
Godet
Yann
Y
Institut National de Santé et de Recherche Médicale, Unité Mixte de Recherche 892, 44093 Nantes, France.
Moreau-Aubry
Agnès
A
Guilloux
Yannik
Y
Vignard
Virginie
V
Khammari
Amir
A
Dreno
Brigitte
B
Jotereau
Francine
F
Labarriere
Nathalie
N
D019264:Adoptive Transfer; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D018189:Immunomagnetic Separation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D009841:Oligonucleotides; D012008:Recurrence; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D000951:Antigens, Neoplasm; D017931:DNA Primers; D018076:DNA, Complementary; C533520:MELOE-1 antigen, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D009841:Oligonucleotides